Platelets are small and numerous cells, second only to red blood cells in the bloodstream. They have been recognized mainly for their contributions to blood clotting, however, we now know that they also play important roles in our responses to infection and inflammation. In this extensive review, we cover the “classic” platelet receptors involved in blood clotting and “unconventional” immune receptors that platelets possess and how both groups contribute to our immune responses. Platelet receptors can interact with bacteria and affect the behaviors of white blood cells which fight infection. Additionally, these receptors can be involved in autoimmune conditions, when the body mounts an immune response against itself. Continued research on these interactions could lead to development of new treatments against numerous diseases.